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Retinoic acids and trichostatin A (TSA), a histone deacetylase inhibitor, induce human pyruvate dehydrogenase kinase 4 (PDK4) gene expression.

Authors :
Kwon HS
Huang B
Ho Jeoung N
Wu P
Steussy CN
Harris RA
Source :
Biochimica et biophysica acta [Biochim Biophys Acta] 2006 Mar-Apr; Vol. 1759 (3-4), pp. 141-51. Date of Electronic Publication: 2006 Apr 27.
Publication Year :
2006

Abstract

Induction of pyruvate dehydrogenase kinase 4 (PDK4) conserves glucose and substrates for gluconeogenesis and thereby helps regulate blood glucose levels during starvation. We report here that retinoic acids (RA) as well as Trichostatin A (TSA), an inhibitor of histone deacetylase (HDAC), regulate PDK4 gene expression. Two retinoic acid response elements (RAREs) to which retinoid X receptor alpha (RXRalpha) and retinoic acid receptor alpha (RARalpha) bind and activate transcription are present in the human PDK4 (hPDK4) proximal promoter. Sp1 and CCAAT box binding factor (CBF) bind to the region between two RAREs. Mutation of either the Sp1 or the CBF site significantly decreases basal expression, transactivation by RXRalpha/RARalpha/RA, and the ability of TSA to stimulate hPDK4 gene transcription. By the chromatin immunoprecipitation assay, RA and TSA increase acetylation of histones bound to the proximal promoter as well as occupancy of CBP and Sp1. Interaction of p300/CBP with E1A completely prevented hPDK4 gene activation by RXRalpha/RARalpha/RA and TSA. The p300/CBP may enhance acetylation of histones bound to the hPDK4 promoter and cooperate with Sp1 and CBF to stimulate transcription of the hPDK4 gene in response to RA and TSA.

Details

Language :
English
ISSN :
0006-3002
Volume :
1759
Issue :
3-4
Database :
MEDLINE
Journal :
Biochimica et biophysica acta
Publication Type :
Academic Journal
Accession number :
16757381
Full Text :
https://doi.org/10.1016/j.bbaexp.2006.04.005